Association analysis of copy numbers of FC-gamma receptor genes for rheumatoid arthritis and other immune-mediated phenotypes

摘要: Segmental duplications (SDs) comprise about 5% of the human genome and are enriched for immune genes. SD loci often show copy numbers variations (CNV), which difficult to tag with genotyping methods. CNV in Fc gamma receptor region (FCGR) has been suggested be associated rheumatic diseases. The objective this study was delineate association FCGR-CNV rheumatoid arthritis (RA), coeliac disease Inflammatory bowel incidence. We developed a method accurately quantify based on intensity values from Immunochip platform applied it FCGR locus. determined method's validity using three independent assays: segregation analysis families, arrayCGH, whole sequencing. Our data showed presence two separate CNVs first encodes FCGR2A, FCGR3A part FCGR2C gene, second another FCGR2C, FCGR3B FCGR2B. Analysis status 4578 individuals RA 5457 controls indicated gene antibody-negative (P = 0.002, OR 1.43). Deletion increased risk antibody-positive RA, consistently previous reports 0.023, 1.23). A clear genotype-phenotype relationship observed: polymorphisms correlated CD16A expression (encoded by FCGR3A) CD8 T-cells. In conclusion, our allows determining locus, we identified functional between expression.